The complex interplay of genetics, epigenetics, and environment in the predisposition to alcohol dependence

alcohol dependence is a major global problem, associated with lower quality of physical and mental health, higher mortality and an enormous familial and social cost. prevention strategies and treatment of this condition are therefore crucial. success of psychosocial programs and pharmacological treatments has been frequently reported, but a better understanding of the etiology of this chronic disease is needed. for this purpose, the identification of associated factors in different populations is of great significance. it has been clearly demonstrated by twin and adoption studies and supported by animal models that both genetic and environmental components play a substancial role in alcohol dependence. heritabil ity estimates range from 40 to 60%, depending on the specific analyzed sample. several coexisting genetic variants in each affected individual, rather than a single gene transmitted in a mendelian manner, may be the rule in alcohol dependence. similarly, many environmental factors can increase susceptibility, and because of their diversity, they do not have to be the same in every affected person. environmental contribution may be linked to epigenetics, which refers to chemical processes that can modify gene activity without changing the sequence of dna. in humans, the most stable epigenetic process is the union of a methyl group (one carbon atom surrounded by three hydrogen atoms) to cytosines in dna. other epigenetic mechanisms are modifications to nuclear proteins called histones, which alter the way dna is packed. moreover, non-protein coding rnas such as micrornas have been associated with the development of alcohol dependence. micrornas could work as epigenetic intermediaries that allow ethanol to affect complex and divergent developmental mechanisms, which is added to the effect of dna methylation, histone acetylation, and other epigenetic modifications. most reasearch points to an association between alcohol dependence and genes related with alcohol